Functional genomics of UV radiation responses in human cells

被引:47
作者
Koch-Paiz, CA
Amundson, SA
Bittner, ML
Meltzer, PS
Fornace, AJ [1 ]
机构
[1] NCI, Gene Response Sect, Ctr Canc Res, Bethesda, MD 20892 USA
[2] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA
关键词
UV irradiation; cDNA microarray hybridization; cell signaling; suramin;
D O I
10.1016/j.mrfmmm.2004.01.010
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The gene expression responses of MCF-7, a p53 wild-type (wt) human cell line, were monitored by cDNA microarray hybridization after exposure to different wavelengths of UV irradiation. Equitoxic doses of UVA, UVB, and UVC radiation were used to reduce survival to 37%. The effects of suramin, a signal pathway inhibitor, on the gene expression responses to the three UV wavelengths were also compared in this model system. UVB radiation triggered the broadest gene expression responses, and 172 genes were found to be consistently responsive in at least two-thirds of independent UVB experiments. These UVB radiation-responsive genes encode proteins with diverse cellular roles including cell cycle control, DNA repair, signaling. transcription, protein synthesis, protein degradation, and RNA metabolism. The set of UVB-responsive genes included most of the genes responding to an equitoxic dose of UVC radiation, plus additional genes that were not strongly triggered by UVC radiation. There was also some overlap with genes responding to an equitoxic dose of UVA radiation, although responses to this lower energy UV radiation were overall weaker. Signaling through growth factor receptors and other cytokine receptors was shown to have a major role in mediating UV radiation stress responses, as suramin, which inhibits such receptors, attenuated responses to UV radiation in nearly all the cases. Inhibition by suramin was greater for UVC than for UVB irradiation. This probably reflects the more prominent role in UVB damage response of signaling by reactive oxygen species, which would not be affected by suramin. Our results with suramin demonstrate the power of cDNA microarray hybridization to illuminate the global effects of a pharmacologic inhibitor on cell signaling. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:65 / 78
页数:14
相关论文
共 42 条
  • [1] Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light
    Abe, T
    Oue, N
    Yasui, W
    Ryoji, M
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 310 (04) : 1168 - 1174
  • [2] Genomic interrogation of mechanism(s) underlying cellular responses to toxicants
    Amin, RP
    Hamadeh, HK
    Bushel, PR
    Bennett, L
    Afshari, CA
    Paules, RS
    [J]. TOXICOLOGY, 2002, 181 : 555 - 563
  • [3] Amundson SA, 2000, RADIAT RES, V154, P342, DOI 10.1667/0033-7587(2000)154[0342:IOPMBI]2.0.CO
  • [4] 2
  • [5] Functional genomics as a window on radiation stress signaling
    Amundson, SA
    Bittner, M
    Fornace, AJ
    [J]. ONCOGENE, 2003, 22 (37) : 5828 - 5833
  • [6] Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses
    Amundson, SA
    Bittner, M
    Chen, YD
    Trent, J
    Meltzer, P
    Fornace, AJ
    [J]. ONCOGENE, 1999, 18 (24) : 3666 - 3672
  • [7] A nucleotide excision repair master-switch: p53 regulated coordinate induction of global genomic repair genes
    Amundson, SA
    Patterson, A
    Do, KT
    Fornace, AJ
    [J]. CANCER BIOLOGY & THERAPY, 2002, 1 (02) : 145 - 149
  • [8] AMUNDSON SA, 2003, COMPLEXITY STRESS SI, V3, P179
  • [9] Amundson Sally A, 2003, Methods Mol Biol, V223, P141
  • [10] Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells
    Burczynski, ME
    McMillian, M
    Ciervo, J
    Li, L
    Parker, JB
    Dunn, RT
    Hicken, S
    Farr, S
    Johnson, MD
    [J]. TOXICOLOGICAL SCIENCES, 2000, 58 (02) : 399 - 415